The objective of the project is to accelerate discovery and a new program for multidisciplinary interaction across cognitive neuroscience, human neuroimaging and medicine at the University of Washington (UW). The project uses the infrastructure of the Integrated Brain Imaging Center to partner with existing established Centers and groups whose scientific programs can immediately investigate basic and translational questions in neurodegenerative disease, brain aging, epilepsy, and rehabilitation of paralysis with new systems neuroimaging approaches. The UW is a premier biomedical research institution and a particularly strong institutional setting for using imaging to elucidate biological mechanisms and biomarkers of disease, and for conducting translational studies. The theme of this proposal is the application of emerging systems neuroimaging approaches to key basic problems in neurologic disease pathophysiology, and key translational settings. One project cluster centers around novel uses of systems neuroimaging and MR spectroscopy to understand mechanisms in degenerative disease (Alzheimer disease, Parkinson disease). One goal is to understand and detect the early vulnerability of the default mode network in Alzheimer disease. For this work, we will use two subject groups: well characterized mild cognitive impairment, which often reflects incipient Alzheimer disease, and aging individuals who have been rigorously stratified with respect to their cognitive trajectories in midlife and old age. A second goal is to understand cognitive impairments in Parkinson disease, which arise in the setting of disturbances primarily in ascending systems. A third goal is understanding factors governing prognosis for language and other cognitive impairments after epilepsy surgery. A second cluster project cluster is driven by outstanding UW expertise in human neurophysiology, electrophysiology and sensorimotor engineering, and focuses on integration of imaging with electrophysiology to understand the neurophysiologic dynamics of clinically relevant large scale systems (default mode network, dorsal attentional network), and to improve brain-computer interfaces for rehabilitation of paralysis. For each collaboration we propose an initial high impact study and future directions. PUBLIC HEALTH RELEVANCE: This project will develop new collaborative scientific teams at the University of Washington to work in partnership with the Integrated Brain Imaging Center and apply new imaging methods to degenerative dementia, brain aging, epilepsy, and rehabilitation of paralysis. One cluster of projects will investigate the biological basis of early Alzheimer disease, disorders of attention and concentration in Parkinson disease, and language problems in epilepsy surgery. A second cluster of projects will used EEG and imaging to understand signaling in brain systems and how to extract signals for controlling brain-computer interfaces. )